Homotypic interactions mediated by slamf1 and slamf6 receptors control NKT cell lineage development
Homotypic interactions mediated by slamf1 and slamf6 receptors control NKT cell lineage development
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DOI：
10.1016/j.immuni.2007.08.020
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发表时间：
2007-11-01
期刊：
影响因子：
32.4
通讯作者：
Bendelac, Albert
中科院分区：
文献类型：
--
作者：
Griewank, Klaus;Borowski, Christine;Bendelac, Albert
在α β T细胞受体（TCR）介导的共同前体与胸腺中的配体表达细胞的相互作用期间确定对T和自然杀伤T（NKT）细胞谱系的定型。而主流胸腺细胞前体识别基质细胞表达的主要组织相容性复合体（MHC）配体，NKT细胞前体与皮质胸腺细胞表达的CD 1d配体相互作用。在这里，我们证明了这种同型T-T相互作用产生的“第二信号”介导的同嗜性受体Slamf 1（SLAM）和Slamf 6（Ly 108）的合作参与和下游的衔接子SLAM相关蛋白（SAP）和Src激酶Fyn的招聘，这是必不可少的谱系扩增和分化的NKT细胞谱系。这些受体相互作用是TCR参与过程中所必需的，因此仅在选择配体由胸腺细胞而不是不表达Slamf 6或Slamf 1的上皮细胞呈递时发生。因此，NKT细胞配体识别的拓扑结构决定了NKT细胞谱系发育所必需的共信号通路的可用性。
Commitment to the T and natural killer T (NKT) cell lineages is determined during alpha beta T cell receptor (TCR)-mediated interactions of common precursors with ligand-expressing cells in the thymus. Whereas mainstream thymocyte precursors recognize major histocompatibility complex (MHC) ligands expressed by stromal cells, NKT cell precursors interact with CD1d ligands expressed by cortical thymocytes. Here, we demonstrated that such homotypic T-T interactions generated "second signals" mediated by the cooperative engagement of the homophilic receptors Slamf1 (SLAM) and Slamf6 (Ly108) and the downstream recruitment of the adaptor SLAM-associated protein (SAP) and the Src kinase Fyn, which are essential for the lineage expansion and differentiation of the NKT cell lineage. These receptor interactions were required during TCR engagement and therefore only occurred when selecting ligands were presented by thymocytes rather than epithelial cells, which do not express Slamf6 or Slamf1. Thus, the topography of NKT cell ligand recognition determines the availability of a cosignaling pathway that is essential for NKT cell lineage development.